**4. Conclusions**

The increasing evidence of the role of gu<sup>t</sup> microbiota in the development, maintenance and disruption of the immune system comes from animal and human studies. The liver, as a key organ in local and systemic immunity maintenance, is in strict contact with microbial antigens and gu<sup>t</sup> microbiota derangement has a direct or indirect causative role on the development and progression of several liver diseases (Table 1). Thus, microbiota modulation consisting in the use of probiotics seems an appealing instrument for a safe immunity re-shaping in liver diseases.

Gut virome modulation on liver and systemic immunity for the treatment of viral- and immune-mediated hepatitis and hepatocellular carcinoma are more than promising. However, randomized controlled trials are needed to confirm animal and preliminary human studies. Understanding in depth the immunomodulatory role of the gu<sup>t</sup> microbiota and virome in health and disease is also of prime importance to counteract pandemics such as that caused by the ongoing SARS-CoV-2 infection, as COVID-19-a ffected patients show not only respiratory distress syndrome but also multiorgan dysfunction including the liver.

**Author Contributions:** L.A. and E.S. had the original idea for the review article; L.A. and E.S. performed the review of literature; C.R., E.R., T.L. and F.L. reviewed the literature findings; E.S. and L.A. wrote the manuscript; S.F., P.R. and I.A. critically revised the manuscript; S.F. revised the English form. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** Authors declare no financial conflict of interests.
